The cell adhesive glycoprotein fibronectin (FN) is deposited in specific pathways during embryogenesis that are followed by migrating cells, and as part of the extracellular matrix in most organs. Blocking the interaction of embryonic cells with FN causes profound disturbances in development. In adults, circulating plasma FN is synthesized by the liver, but little appears to be synthesized in other tissues. However, during wound repair FN expression is coordinately increased along with other connective tissue components, possibly as a result of polypeptide growth factors such as transforming growth factor beta that stimulate FN and FN receptor expression and that also act during embryogenesis. Cells transformed with oncogenic viruses typically lose their FN matrices, and this disturbance in cell-matrix interaction may be responsible for some abnormalities of the transformed phenotype, including even metastasis. Cells interact with FN-containing matrices via specific transmembrane receptors in the VLA subfamily of integrins. However, we have shown that the deposition of FN matrices requires the specific binding of cells to an aminoterminal site in FN distinct that interacting with adhesive cellular receptors. Thus, two separate systems of cellular interactions with FN exist, one for deposition and the other for recognition. Because FN-containing matrices appear to play such a vital role in growth, development, wound healing and possible tumor metastasis, it is important to understand how they are deposited. To do this, we plan to: 1) Isolate and characterize the cell surface molecules interacting with FN's aminoterminal 29 kDa matrix assembly domain. 2) Study structure-function relationships in the aminoterminal matrix assembly domain using recombinant DNA. 3) Elucidate the role of FN's matrix assembly and cell adhesive domains in binding to cells, and determine if deficient binding of FN's aminoterminal matrix assembly domain accompanies oncogenic transformation.